Tumour necrosis factor receptor-associated periodic syndrome (TRAPS)

The estimated prevalence is 1/1,000,000 worldwide.

TRAPS is inherited in an autosomal dominant manner. Each child of an affected individual has a 50% risk of inheriting the pathogenic variant. Prenatal molecular testing is technically possible once the familial pathogenic variant has been identified.

The diagnosis of TRAPS rests on recurrent inflammatory episodes consistent with the clinical phenotype, supported by laboratory evidence of systemic inflammation (elevated C-reactive protein, serum amyloid A, and erythrocyte sedimentation rate) during flares, and confirmed by identification of a heterozygous pathogenic variant in TNFRSF1A. The Eurofever/PRINTO classification criteria provide a validated framework that integrates clinical features with molecular findings; fulfilment of these criteria establishes the clinical diagnosis of TRAPS.

Main differential diagnoses include:

• : recurrent short episodes of inflammation and serositis, including fever, peritonitis, synovitis, pleuritis, and (rarely) pericarditis; MEFV
• Hyperimmunoglobulin D and (HIDS): recurrent attacks of fever, abdominal pain, and arthralgia often brought on by stress or vaccination; MVK
• Muckle-Wells syndrome (MWS): urticaria, deafness, and renal amyloidosis; NLRP3

• Establishing or confirming the clinical diagnosis at the molecular level.
• Enabling specific and individualised surveillance and clinical management as a prerequisite for targeted medical care, with decisions made by the treating physicians in consultation with the affected individual.
• Testing of family members at risk, where this is desired and clinically appropriate following genetic counselling.

• Deuitch N, Cudrici C, Ombrello A, Aksentijevich I. TNF receptor-associated periodic fever syndrome. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. PMID: .
• Gattorno M, Hofer M, Federici S, Vanoni F, Bovis F, Aksentijevich I, et al. Classification criteria for autoinflammatory recurrent fevers. Ann Rheum Dis. 2019;78(8):1025-1032. PMID: .
• Cudrici C, Deuitch N, Aksentijevich I. Revisiting TNF receptor-associated periodic syndrome (TRAPS): current perspectives. Int J Mol Sci. 2020;21(9):3263. PMID: .